We propose to test the hypothesis that the composition of dietary lipid determines, in part, the response of lung cells to oxidant stress. The probable mechanism involves alteration of tissue fatty acid profiles with a subsequent effect on the synthesis, degradation and endogenous concentrations of prostaglandins, thromboxanes and related metabolites. The long-term goal toward which this proposed work would contribute is the development of a diet optimum for use by humans to tolerate oxidant stress. The specific objectives of the proposed work are to: a) evaluate the qualitative and quantitative changes in non-surfactant tissue fatty acid profiles as a function of dietary polyunsaturated fatty acid (PUFA) intake, b) describe changes in lung fatty acid profiles during exposure to hyperoxia, c) determine lung synthetic potential and endogenous concentrations of selected prostaglandins, thromboxanes and related metabolites as a function of dietary lipid composition and during oxygen exposure, and d) assess any variations in the onset of pulmonary toxicity as a function of dietary lipid composition, lung fatty acid profiles and prostaglandin metabolism. Weanling rats will be fed a semi-synthetic diet containing 21.2% fat with PUFA ranging from essential fatty acid deficiency to supranormal levels, with balance as saturated fat. The fatty acid profiles of the major lipid classes of non-surfactant lung tissue will be analyzed as will be the prostaglandin synthetic potential and endogenous concentrations of prostaglandins. The same parameters will also be measured in rats fed different diets and exposed to hyperoxia. The relative susceptibility to oxidant stress of rats fed various diets will be compared using the activity of combined prostaglandin dehydrogenase/reductase, a sensitive biochemical indicator of oxygen toxicity.